Compositions having a physiological cooling effect

ABSTRACT

Alkyl-substituted methanols are disclosed having the property of stimulating the cold receptors of the nervous system of the human body to produce a cold sensation and are used for this purpose in a variety of edible and topical preparations.

FIELD OF INVENTION

This invention relates to compositions and compounds having aphysiological cooling effect on the skin and on the mucous membranes ofthe body, particularly those of the mouth, nose, throat andgastrointestinal tract.

BACKGROUND OF THE INVENTION AND PRIOR ART

Menthol is well known for its physiological cooling effect on the skinand mucous membranes of the mouth and has been extensively used as aflavouring agent (menthol being a major constituent of oil ofpeppermint) in foodstuffs, beverages, dentifrices, mouthwashes, etc. andas a component in a wide range of toiletries, liniments and lotions fortopical application. Menthol is also a well known tobacco additive forproducing a `cool` sensation in the mouth when smoking.

It is well established that the `cooling` effect of menthol is aphysiological effect due to the direct action of menthol on the nerveendings of the human body responsible for the detection of hot or coldand is not due to latent heat of evaporation. It is believed that thementhol acts as a direct stimulus on the cold receptors at the nerveendings which in turn stimulate the central nervous system.

Although menthol is well established as a physiological coolant its use,in some compositions, is circumscribed by its strong minty odour and itsrelative volatility.

A few other compounds have been reported in the technical literature ashaving an odour or flavour similar to menthol and from time to time havebeen proposed as flavourants or odourants in a variety of topical andingestible compositions. For example, Japanese Patent Publication No.39-19627 reports that 3-hydroxymethyl p-menthane (menthyl carbinol) hasa flavour closely resembling that of 1-menthol and suggests its use as aflavourant in confectionery, chewing gum and tobacco. In Swiss Pat. No.484,032 certain saccharide esters of menthol are proposed as additivesto tobacco. In French Pat. No. 1,572,332 N,N-dimethyl 2-ethylbutanamideis reported as having a minty odour and refreshing effect, and the mintyodour of N,N-diethyl 2,2-dimethylpropanamide is also referred to. Asimilar effect is reported for N,N-diethyl 2-ethylbutanamide in Berichte39, 1223, (1906). A minty odour has also been reported for2,4,6-trimethylheptan-4-ol and 2,4,6-trimethyl hept-2-en-4-ol inParfums-Cosmetiques-Savons, May 1956, pp. 17-20. The cooling effect ofmenthol and other related terpene alcohols and their derivatives hasalso been studied and reported in Koryo, 95, (1970), pp. 39-43.2,4-p-menthane diol has also been reported as having a sharp coolingtaste (Beilstein, Handbuch der Organischen Chemie, fourth Ed. (1923)Vol. 6, p. 744.). Still other substituted p-menthanes having aphysiological cooling effect are disclosed in German OffenlegungsschriftNos. P 22 02 535, P 22 03 947, P 22 03 273 and P 22 05 255.

Despite this knowledge of other compounds having an odour and flavoursimilar to that of menthol, menthol is still extensively used intopical, ingestible and other compositions notwithstanding thedisadvantages mentioned above, namely its very strong odour and itsrelative volatility.

OBJECTS OF THE INVENTION

It is an object of the present invention to provide other compoundshaving a pronounced physiological cooling effect, in many cases far morepersistent than that obtained with menthol, without the attendantdisadvantages of a strong minty odour but with alternative odours.

It is a further object to provide compounds having a pronouncedphysiological cooling effect and being of relatively low volatility.

It is a further object of the present invention to provide ingestible,topical and other compositions capable of stimulating the cold receptorsof the nervous system of the human body thereby to create a desirable`cool` sensation, and a method of making them.

It is a yet further object of the present invention to provide a methodof stimulating the cold receptors of the nervous system of the body tocreate a cool sensation.

Other objects will be apparent from the following detailed descriptionof the invention.

SUMMARY OF INVENTION

The present invention is based on the discovery of a group of primaryalcohols which have a pronounced physiological cooling activity, butwhich are without the strong minty odour characteristic of mentholhaving instead rather different odours mainly of a camphoraceous natureand which are of relatively low volatility and which are substantiallynon-toxic. These compounds are primary alcohols of the formula: ##STR1##where R¹ is C₂ -C₆ alkyl;

R² is C₂ -C₅ alkyl; or C₂ -C₅ alkenyl;

R³ is H or C₁ -C₅ alkyl;

with the provisos that

i. the total number of carbon atoms in the molecule is from 8-14,preferably 8-12, inclusive;

ii. R¹ and R² may also be joined to form, together with the carbon atomto which they are attached, a saturated monocyclic hydrocarbon groupcontaining up to 11 ring carbon atoms;

iii. when R¹ and R² are so joined and with the carbon atom to which theyare attached form a p-menthyl group, then R³ is C₁ -C₅ alkyl;

iv. when R¹ and R² are so joined and R³ is H then the carbocyclic ringshall contain at least one alkyl substituent; and

v. when R¹ and R² are separate groups and R³ is H then at least one ofR¹ and R² shall have branching in an alpha or beta position.

STATEMENT OF INVENTION

In accordance with this invention, therefore, there are providedconsumer products for application to or consumption by the human bodycomprising a consumer product base and a means for stimulating the coldreceptors of the nervous system of the human body wherein said meanscomprise an effective amount of one or more primary alcohols of theformula hereinbefore set forth.

By consumer product we mean a manufacturered product applied to orconsumed by the human person for toilet, cosmetic, hygienic, nutritive,curative, prophylactic, or other purposes and constituting a vehicle bymeans of which the said primary alochols may be brought into contactwith the skin, mucous membranes or other surface tissues of the body,whether external tissues or internal, for example, of the nose, throat,mouth and gastrointestinal tract, and includes liquid and solid phasepreparations of an essentially formless nature e.g. solutions,emulsions, pastes, ointments, powders etc., solid phase preparations ofsemi-permanent form, e.g. shaped toilet and cosmetic preparations andshaped edible preparations, whose shaped form is only temporary andwhich lose that form on use, and articles of permanent form but whichare of an essentially disposable nature, e.g. cleansing tissues,toothpicks etc.

Typical consumer products into which the primary alcohols may beincorporated in accordance with this invention and which may thereforeserve as vehicles for application of the compounds to the person are:

1. Edible and potable compositions including alcoholic and non-alcoholicbeverages; confectionary; chewing gum; cachous; ice cream; jellies;

2. Toiletries including after-shave lotions, shaving soaps, creams andfoams, toilet water, deodorants and antiperspirants, `solid colognes`,toilet soaps, bath oils and salts, shampoos, hair oils, talcum powders,face creams, hand creams, sunburn lotions, cleansing tissues,dentifrices, toothpicks, mouthwashes, hair tonics, eyedrops;

3. Medicaments including antiseptic ointments, pile ointments,liniments, lotions, decongestants, counter-irritants, cough mixtures,throat lozenges, antacid and indigestion preparations, oral analgesics;

4. Miscellaneous compositions such as water soluble adhesivecompositions for envelopes, postage stamps, adhesive labels etc.

DETAILED DESCRIPTION

Many of the primary alcohols used in accordance with this invention areknown compounds and some are commercially available. They may, ingeneral be prepared by procedures well known in the art for thepreparation of alcohols, for example, by the reduction, using lithiumaluminium hydride of carboxylic acids, acid chlorides or esters of thetype: ##STR2## where R¹, R² and R³ are as above defined and X is --OH,--Cl or --OR, where R is lower, e.g. C₁ -C₅, alkyl.

Many of the compounds used as cold receptor stimulants in accordancewith this invention exhibit either geometric or optical isomerism orboth and, depending on the starting materials and the methods used intheir preparation the compounds may be isomerically pure, i.e.consisting of one geometric or optical isomer, or they may be isomericmixtures, both in the geometric and optical sense. Generally, thecompounds will be used as isomeric mixtures, but in some cases thecooling effect may differ as between geometric or optical isomers, andtherefore one or other isomer may be preferred.

The cooling sensation created by the compounds used in this invention onthe skin and mucous membranes, for example, in the mouth, varies both inintensity and longevity from compound to compound. Amongst the mostpreferred compounds used in accordance with this invention are cycliccompounds containing 5, 6 or 7 ring carbon atoms, a total of from 10-12carbon atoms and having an alpha-branched C₃ -C₅ alkyl group in a 1 or2-position in the ring. Typical cyclic compounds in this preferred groupare:

(1-isopropyl-2-methylcyclopentyl) methanol

(1-isopropylcycloheptyl) methanol

(1-sec.butylcycloheptyl) methanol

(2-isopropylcycloheptyl) methanol

(1-isopropyl-2-methylcycloheptyl) methanol

(1-isopropylcyclohexyl) methanol.

Preferred acyclic compounds are those containing a total of from 8-12carbon atoms, R³ is H or C₁ -C₅ straight chain alkyl and at least one ofR¹ and R² has branching in an alpha position. Typical acyclic compoundsin this preferred group are

2,2,4-trimethylpent-3-yl methanol

2-methyl-3-ethylpent-3-yl methanol

2,4-dimethylpent-3-yl methanol

2,4-dimethyl-3-ethylpent-3-yl methanol.

For the purposes of the present disclosure the following test procedurehas been devised as a means to identify compounds having a physiologicalcooling activity in accordance with the present invention and hereinreferred to as cold receptor stimulants. This test is intended purely asa means for identifying compounds having a physiological coolingactivity and useful in the present invention and for giving anindication of the different relative activities of the compounds, asbetween themselves and as compared with menthol, when applied in aparticular manner to a particular part of the body. The results are notnecessarily indicative of the activity of these compounds in otherformulations and other parts of the body where other factors come intoplay. For example, a controlling factor in the onset of cooling effect,its intensity and longevity will be the rate of penetration of thecompounds through the epidermis and this will vary in differentlocations on the human body. The formulation of actual productsaccording to this invention will therefore be done largely on anempirical basis although the test results and other figures given hereinwill be useful as a guide, particularly in the formulation of productsfor oral administration, since the test procedure to be describedinvolves oral application of the compound. A similar test may, ofcourse, be devised for the purposes of measuring the relative activitiesof the compounds on another area of the body, for example, the face orforearm, and this will be a useful guide in the choice of compounds tobe used in preparation for external topical usage.

It will also be noted that the described test procedure is done on astatistical basis. This is necessary since sensitivity to thesecompounds will vary not only from compound to compound and from one partof the body to another, but also from one individual to another. Testsof this nature are commonly used in the testing of the organolepticproperties, e.g. taste, smell etc. of organic and inorganic compounds,see Kirk-Othmer: Encyclopedia of Chemical Technology, second Ed. (1967)Vol. 14 pages 336-344.

TEST PROCEDURE

The following test procedure is aimed at determining the minimumquantity of the test compound required to produce a noticeable coolingeffect on a person of average sensitivity, this minimum quantity beingtermed the threshold for that particular compound. The tests are carriedout on a selected panel of 6 people of median sensitivity to 1-menthol.

PANEL SELECTION

To select a test panel of average sensitivity the following procedure isused. Known quantities of 1-menthol in solution in petroleum ether (bp.40-60) are placed on 5 mm squares of filter paper, whereafter thesolvent is allowed to evaporate. A panel of observers is enrolled andasked to place one impregnated square at a time on the tongue and toreport on the presence or absence of a cooling effect. The quantity of1-menthol on each impregnated square is gradually reduced from a valuesubstantially above 0.25 μg. per square to substantially below 0.25 μg,the precise range being immaterial. Conveniently, one starts withsquares containing 2.0 μg 1-menthol, the amount on each successivesquare being half that of the preceding square, i.e. the second testsquare will contain 1.0 μg, the third 0.5 μg and so on. Each quantity istested on the tongue at least 10 times. In this way, the thresholds tocold receptor stimulus by 1-menthol are determined for each individualof the panel, the threshold for each individual being that amount of1-menthol for which, in a series of not less than 10 test applications,a cooling effect is reported 50% of the time. Six panel members are nowselected whose threshold to 1-menthol is in the range 0.1 μg to 10 μgand whose average threshold is approximately 0.25 μg, this select panelbeing regarded as the test panel of average sensitivity.

COMPOUND TESTING

To test the activity of compounds according to this invention, the aboveprocedure is repeated using only the 6 selected panel members of averagesensitivity to 1-menthol. The individual thresholds for each testcompound on each of the 6 selected panel members are determined andaveraged. Those compounds whose average threshold on the select testpanel is 100 μg or less are regarded as having cooling activity inaccordance with this invention.

TEST RESULTS

The following table sets out the relative cooling activities ofcompounds of the formula defined above when tested according to theforegoing procedure.

                  Table                                                           ______________________________________                                                                   Threshold                                          Compound                   (Mg)                                               ______________________________________                                        (2-isopropylcycloheptyl) methanol                                                                        1                                                  2,2,4-trimethylpent-3-yl methanol                                                                        1                                                  (1-isopropyl-2-methylcyclopentyl) methanol                                                               2                                                  (1-sec.butylcycloheptyl) methanol                                                                        2                                                  (1-isopropyl-2-methylcycloheptyl) methanol                                                               2                                                  (1-isopropylcycloheptyl) methanol                                                                        4                                                  (1-isopropylcyclohexyl) methanol                                                                         4                                                  (2,2,6-trimethylcyclohexyl) methanol                                                                     5                                                  n-hept-3-yl methanol       5                                                  2,2-dimethyl-hex-5-en-3-yl methanol                                                                      6                                                  2,6,6-trimethylcycloheptyl) methanol                                                                     6                                                  (1,2-diethylcyclohexyl) methanol                                                                         7                                                  2-methyl-3-ethylpent-3-yl methanol                                                                       7                                                  2,4-dimethylpent-3-yl methanol                                                                           8                                                  2,4-dimethyl-3-ethylpent-3-yl methanol                                                                   8                                                  (1-ethyl-2-methylcyclohexyl) methanol                                                                    9                                                  (1-ethylcycloheptyl) methanol                                                                            10                                                 (3-ethyl-p-menth-3-yl) methanol                                                                          15                                                 (3,3,5,5-tetramethylcyclohexyl) methanol                                                                 18                                                 2,4,6-trimethylhept-4-yl methanol                                                                        20                                                 (1-ethylcycloundecyl) methanol                                                                           20                                                 (4-tert.butylcyclohexyl) methanol                                                                        20                                                 (1-n-butyl-2,3-dimethylcyclohexyl) methanol                                                              50                                                 3,4,5-trimethylhept-4-yl methanol                                                                        50                                                 ______________________________________                                    

The cold receptor stimulants used in this invention find utility in awide variety of consumer products for consumption by or application tothe human body. Broadly speaking, these products can be divided intoingestibles and topicals, both terms being taken in their broadestpossible sense. Thus ingestible is to be taken as including not onlyfoodstuffs and beverages taken into the mouth and swallowed, but alsoother orally ingested products taken for reasons other than theirnutritional value, e.g. indigestion tablets, antacid preparations,laxatives, etc. Ingestible is also to be taken to include ediblecompositions taken by mouth, but not necessarily swallowed, e.g. chewinggum. Topical is to be taken as including not only compositions such asperfumes, powders and other toiletries, lotions, linaments, oils andointments, applied to the external surfaces of the human body, whetherfor medical or other reasons, but also compositions applied to, orwhich, in normal usage, come in contact with, internal mucous membranesof the body, such as those of the nose, mouth or throat, whether bydirect or indirect application, mouthwash and gargle compositions.Topical products, in this context, also include toilet articles such ascleansing tissues and toothpicks.

In formulating the products of this invention the cold receptorstimulants will be incorporated into a vehicle by means of which thecompound may be applied to the person. The vehicle may, itself becompletely inert or it may, and usually will, contain other activeingredients. A wide variety of vehicles will be suitable, depending uponthe particular product involved, such vehicles including solids,liquids, emulsions, foams and gels. Typical vehicles for the coldreceptor stimulants include aqueous or alcoholic solutions, oils andfats such as hydrocarbon oils, fatty acid esters, long chain alcoholsand silicone oils; finely divided solids such as starch or talc;cellulosic materials such as paper tissue; low-boiling hydrocarbons andhalohydrocarbons used as aerosol propellants; gums and natural orsynthetic resins.

Generally, these vehicles will contain at least one or more of thefollowing adjuvants: flavourants, colourants, perfuming agents, surfaceactive agents, antiseptic agents, such as are usually employed intopical and ingestible compositions.

A more detailed discussion of particular products according to thisinvention follows.

TOILETRIES AND COSMETICS

A major area of utility of the cold receptor stimulants of thisinvention will be in the field of toilet preparations broadly classed aspersonal care products. These may be defined as manufactured productsapplied to the person for the purposes of grooming or hygiene or forcosmetic purposes, including make up and perfumery, but excludingethical and proprietary medical preparations. Particular personal careproducts are discussed hereinafter by way of example and are illustratedhereinafter in the specific examples.

One class of personal care product into which the compounds of thisinvention may be incorporated is represented by lotions for topicalapplication, e.g. after-shave lotions, toilet water etc. where thecompound will be used in alcoholic or aqueous alcoholic solution, suchsolutions usually also containing a perfume or mild antiseptic or both.The amount of compound added to the formulation will usually be in therange 0.1 to 10% by weight based on the total composition.

Another class of personal care product is represented by soap andsoap-based compositions where the compounds will be used in combinationwith an oil or fat or a natural or synthetic surfactant e.g. a fattyacid salt or a laurylsulphate salt, the composition usually alsocontaining an essential oil or perfume. The range of soap compositionswill include soaps of all kinds e.g. toilet soaps, shaving soaps,shaving foams etc. particularly shaving foams of the aerosol type.Usually the compound will be added to the formulation in amount of from1 to 10% by weight.

A further class of personal care products into which the cold receptorstimulants may be incorporated is represented by cosmetic creams,emollients and lotions, such creams, emollients and lotions usuallycomprising an oil-in-water emulsion as a base and optionally containinga range of other ingredients such as wax, preservative, perfume,antiseptics, astringents, pigments etc. Also included within this classare lipstic compositions, such compositions usually comprising an oiland wax base into which the coolant can be incorporated along with otheringredients e.g. pigments. Once again the formulation of such products,apart from the incorporation of the cold receptor stimulant, usually inan amount of from 0.05 to 10% by weight, is conventional.

Personal care products for oral hygiene into which the cold receptorstimulants of this invention can be incorporated include mouthwash,gargle and dentifrice compositions. The first two may be consideredtogether and will usually comprise an aqueous, alcoholic oraqueous-alcoholic solution of an antiseptic often coloured or flavouredfor palatability, to which the cold receptor stimulant is added in anamount of from 0.01 to 10% by weight.

Dentifrice compositions may be of the solid block, powder, paste orliquid type and will usually comprise a finely divided abrasive orpolishing material, e.g. precipitated chalk, silica, magnesium silicate,aluminium hydroxide or other similar materials well known in the art,and a detergent or foaming agent. Optional ingredients which may also beincluded are flavouring agents and colourants, antiseptics, lubricants,thickeners, emulsifiers or plasticizers. The amount of cold receptorstimulant added in such compositions will generally be from 0.1 to 5.0%by weight based on the total composition.

EDIBLE AND POTABLE COMPOSITIONS

The cold receptor stimulants of this invention may be incorporated intoa wide range of edible and potable compositions comprising an edible orpotable base and usually one or more flavouring or colouring agents. Theparticular effect of the cold receptor stimulant is to create a cool orfresh sensation in the mouth, and in some cases, even in the stomach,and therefore the compounds find particular utility in sugar-basedconfectionary such as chocolate, boiled sweets, mints and candy, in icecream and jellies and in chewing gum. The formulation of suchconfections will be by traditional techniques and according toconventional recipes and as such forms no part of this invention. Thecold receptor stimulant will be added to the recipe at a convenientpoint and in amount sufficient to produce the desired cooling effect inthe final product. As already indicated, the amount will vary dependingupon the particular compound, the degree of cooling effect desired andthe strength of other flavourants in the recipe. For general guidance,however, amounts in the range 0.1 to 5.0% by weight based on the totalcomposition will be found suitable.

Similar considerations apply to the formulation of beverages. Generallyspeaking the compounds will find most utility in soft drinks, e.g. fruitsquashes, lemonade, cola etc., but may also be used in alcoholicbeverages. The amount of compound used will generally be in the range0.05 to 2.5% by weight based on the total composition.

MEDICAMENTS

Because of their cooling effect on the skin and on the mucous membranesof the mouth, throat and nose and of the gastrointestinal tract the coldreceptor stimulants may be used in a variety of oral medicines, nasaland throat sprays, and topical compositions, particularly where acounter-irritant is required. Generally speaking, these medicalpreparations, whether topical or ingestible proprietary or ethical, willcontain a pharmaceutically acceptable carrier, either liquid or solid, apharmaceutically active ingredient and into these preparations the coldreceptor stimulants of this invention can readily be incorporated toprovide a pleasant cooling effect on the skin, or other surface tissuesof the body, or in the mouth or gastrointestinal tract depending onparticular preparation and whether it is to be applied externally orinternally. A particular utility for the compounds of this invention isin the formulation of antacid and indigestion remedies, and especiallythose based on sodium bicarbonate, magnesium oxide, calcium or magnesiumcarbonate, aluminium or magnesium hydroxide or magnesium trisilicate. Insuch compositions the compound will usually be added in an amount offrom 0.1 to 2.0% by weight.

The cold receptor stimulants may also be included in oral analgesiccompositions e.g. with acetyl salicylic acid or its salts, and in nasaldecongestants e.g. those containing ephedrine.

Consumer products according to the invention are illustrated by thefollowing Examples in which all percentages are by weight.

EXAMPLE 1 After Shave Lotion

An after shave lotion was prepared according to the following recipe bydissolution of the ingredients in the liquid and cooling and filtering:

    ______________________________________                                        Denatured ethanol      75%                                                    Diethylphthalate       1.0%                                                   Propylene Glycol       1.0%                                                   Lactic Acid            1.0%                                                   Perfume                3.0%                                                   Water                  to 100%                                                ______________________________________                                    

Into the base lotion was added 3% by weight based on the totalcomposition of 2,4-dimethylpent-3-yl methanol.

When the final lotion is applied to the face a clearly noticeablecooling effect becomes apparent after a short interval of time.

EXAMPLE 2 Eye Lotion An eye lotion was prepared containing the followingingredients:

    ______________________________________                                        Witch Hazel           12.95%                                                  Boric Acid            2.00%                                                   Sodium Borate         0.50%                                                   Allantoin             0.05%                                                   Salicylic Acid        0.25%                                                   Chlorobutol           0.02%                                                   Zinc Sulphate         0.004%                                                  Water                 to 100%                                                 ______________________________________                                    

To the formulation was added 0.01% based on the total composition, of2-methyl-3-ethylpent-3-yl methanol. When used to bathe the eyes a coolfresh sensation is apparent on the eyeball and eyelids.

EXAMPLE 3 Toothpaste

The following ingredients were mixed in a blender;

    ______________________________________                                        Dicalcium Phosphate      48.0%                                                Sodium Lauryl Sulphate   2.5%                                                 Glycerol                 24.8%                                                Sodium Carboxymethyl Cellulose                                                                         2.0%                                                 Citrus Flavourant        1.0%                                                 Sodium Saccharin         0.5%                                                 Water                    to 100%                                              ______________________________________                                    

Shortly before completion of the blending operation 1% by weight of2,4-dimethyl-3-ethylpent-3-yl methanol was added to the blender.

When applied as a toothpaste, a cooling effect is noticed in the mouth.

EXAMPLE 4 Aerosol Shaving Soap

An aerosol shaving soap composition was formulated according to thefollowing recipe:

    ______________________________________                                        Stearic acid           6.3%                                                   Lauric acid            2.7%                                                   Triethanolamine        4.6%                                                   Sodium carboxymethyl                                                          cellulose              0.1%                                                   Sorbitol               5.0%                                                   Perfume                0.4%                                                   Water                  to 100%                                                ______________________________________                                    

The composition was prepared by fusing the acids in water, adding thetriethanolamine, cooling and adding the other constituents. To themixture was then added 2%, based on the total composition of(1-isopropylcyclohexyl) methanol. The composition was then packaged inan aerosol dispenser under pressure of a butane propellant.

When used in shaving a fresh cool sensation was distinctly noticeable onthe face.

EXAMPLE 5 Toilet Water

A toilet water was prepared according to the following recipe:

    ______________________________________                                        Denatured ethanol      75.0%                                                  Perfume                5.0%                                                   Water                  to 100%                                                ______________________________________                                    

To the recipe was added 4.0% based on the total composition, of2,4-dimethyl-3-ethylpent-3-yl methanol.

As with the after shave lotion, a cooling effect was clearly noticeableon the skin well after the termination of any cooling effectattributable to the evaporation of the alcoholic carrier.

EXAMPLE 6 Soft Sweet

Water was added to icing sugar at 40° C to form a stiff paste. 1.0% of2,4-dimethylpent-3-yl methanol was then stirred into the paste and themixture allowed to set. A soft sweet mass resulted having thecharacteristic cooling effect in the mouth of peppermint but without theminty flavour or odour.

EXAMPLE 7 Indigestion Tablet

The following ingredients were ground together:

    ______________________________________                                        Magnesium carbonate     49.5%                                                 Sorbitol                49.4%                                                 Saccharin                0.1%                                                 Talc                     1.0%                                                 ______________________________________                                    

Added to the mixture during grinding was 0.10% of(1-isopropylcyclohexyl) methanol. After mixing the mixture was pressedinto 0.5 g tablets. Taken by mouth and swallowed the tablets produced,after a short interval of time, a noticeable cooling effect in thestomach.

EXAMPLE 8 Cleansing Tissue

A cleansing liquid was prepared having the formulation:

    ______________________________________                                        Triethanolamine lauryl sulphate                                                                      1.0%                                                   Glycerol               2.0%                                                   Perfume                0.95%                                                  Water                  to 100%                                                ______________________________________                                    

To this liquid was added 4% of 2,4,6-trimethyl-hept-4-yl methanol. Apaper tissue was then soaked in the liquid.

When the impregnated tissue was used to wipe the skin a fresh coolsensation developed on the skin after a short interval.

EXAMPLE 9 Hydrophilic Ointment

A hydrophilic ointment was prepared having the following formulation:

    ______________________________________                                        Propylene Glycol       12%                                                    1-Octadecanol          25%                                                    White Soft Paraffin    25%                                                    Sodium lauryl sulphate  1%                                                    Water                  to 100%                                                ______________________________________                                    

The sodium lauryl sulphate was added to the water and heated to 60° C.The paraffin was melted by heating to 60° C and was then added to thesodium lauryl sulphate mixture with stirring. Propylene glycol and1-octadecanol were then added to this mixture.

To the resultant mixture was added 3% of (1-isopropylcyclohexyl)methanol. The final ointment when applied to the skin gave rise to amarked cooling effect.

EXAMPLE 10 Vapour Rub

4% of (1-isopropyl-2-methylcyclopentyl) methanol was mixed into 96%, ofsoft white paraffin. When rubbed onto the skin a pleasant cooling vapouris released.

EXAMPLE 11 Deodorant Composition

A deodorant composition suitable for formulation and dispensing as anaerosol under pressure of a suitable propellant was formulated accordingto the following recipe:

    ______________________________________                                        Denatured ethanol   96.9%                                                     Hexachlorophene    2.0%                                                       Isopropyl myristate                                                                              1.0%                                                       Perfume            0.1%                                                       ______________________________________                                    

To the composition was added 4% by weight of (2-isopropylcycloheptyl)methanol. Application of the final composition gave rise to a definitecooling sensation on the skin.

EXAMPLE 12 Hair Shampoo

Sodium lauryl ether sulphate, 10 g, was dispersed in 90 g water in ahigh speed mill. To the dispersion was added 4.5% by weight of(1-sec.butylcycloheptyl) methanol. When the hair is washed using theshampoo, a fresh, cool sensation is noticed on the scalp.

EXAMPLE 13 Lipstick

0.1% by weight of 2,2,4-trimethylpent-3-yl methanol was incorporatedinto a proprietary lipstick by melting the lipstick, adding thecompound, and allowing the lipstick to resolidify. When applied to thelips a persistant cooling effect is clearly noticeable.

EXAMPLE 14 Solid Cologne

A solid cologne was formulated according to the following recipe:

    ______________________________________                                        Denatured ethanol      74.5%                                                  Propylene glycol       3.0%                                                   Sodium stearate        5.0%                                                   Perfume                5.0%                                                   Water                  to 100%                                                ______________________________________                                    

The sodium stearate was dissolved by stirring in a warm mixture of theethanol, propylene glycol and water. To the solution was added theperfume and 4% of (1-isopropylcyclohexyl) methanol and the mixture thenallowed to solidify into a waxy cake.

When applied to the forehead a strong cooling effect is obtained.

EXAMPLE 15 Hair Tonic

A hair tonic was formulated containing:

    ______________________________________                                        Denatured ethanol      84.5%                                                  Caster Oil             14.0%                                                  Resorcinol             0.5%                                                   Perfume                1.0%                                                   ______________________________________                                    

The caster oil, resorcinol and perfumes were dissolved in the ethanolcomponent and to the solution was added 4% of1-ethyl-2-methylcyclohexyl) methanol. When rubbed on the scalp a coolingeffect is noticed.

EXAMPLE 16 Mouthwash

A concentrated mouthwash composition was prepared according to thefollowing recipe:

    ______________________________________                                        Ethanol                3.0%                                                   Borax                  2.0%                                                   Sodium bicarbonate     1.0%                                                   Glycerol               10.0%                                                  Flavourant             0.4%                                                   Thymol                 0.03%                                                  Water                  to 100%                                                ______________________________________                                    

To the composition was added 0.5% of (2,2,6-trimethylcyclohexyl)methanol.

When diluted with approximately 10 times its own volume of water andused to rinse the mouth a strong cooling effect is obtained in themouth.

EXAMPLE 17 Toothpicks

The tip of a wooden toothpick was impregnated with an alcoholic solutioncontaining (1-sec.butylcycloheptyl) methanol in sufficient amount todeposit on the toothpick, 0.1 mg of the alcohol. The impregnatedtoothpick was then dried. When placed on the tongue there is nodetectable taste, however, a distinct cooling effect is noticeable aftera short period of time.

EXAMPLE 18 Talcum Powder

A talcum powder was prepared by grinding together the following:

    ______________________________________                                        Low micron talc         90%                                                   Zinc stearate            5%                                                   Starch                   5%                                                   ______________________________________                                    

In the course of grinding there was added 5% of(2-methyl-1-isopropylcycloheptyl) methanol. A talcum powder having afreshening and cooling effect was obtained.

EXAMPLE 19 Soft Drink

A soft drink concentrate was prepared from the following recipe:

    ______________________________________                                        Pure orange juice    60%                                                      Sucrose              10%                                                      Saccharin            0.2%                                                     Orange flavouring    0.1%                                                     Citric acid          0.2%                                                     Sulphur dioxide      trace amount                                             Water                to 100%                                                  ______________________________________                                    

To the concentrate was added 0.1% of (2-isopropylcycloheptyl) methanol.

The concentrate was diluted with water and tasted. An orange flavourhaving a pleasantly cool after-effect was obtained.

EXAMPLE 20 Chewing Gum

Leaves of a proprietary chewing gum were leached in running water for168 hours to remove all water-soluble flavourants. At the end of theleaching operation the chewing gum base had no detectable minty odour orflavour. The chewing gum base was then kneaded with 0.2% of(2-methyl-1-isopropylcycloheptyl) methanol. When compared with thewater-extracted chewing gum base, the final product showed nodistinguishable change in flavour but showed a marked cooling effect inthe mouth.

The above Examples illustrate the range of compounds and the range ofcompositions included within the present invention. However, they arenot to be taken as limiting the scope of the invention in any way.Numerous other compounds within the general formula will be equallysuitable for use in the compositions of Examples 1-20 and thephysiological cooling effect obtained with the compounds of theinvention will recommend their use in a wide variety of othercompositions where the cooling effect will be of value.

The substituted methanols hereinbefore referred to as cold receptorstimulants in ingestible and topical compositions also find utility ascold receptor stimulants in tobacco and tobacco-containing manufactures.

As has already been mentioned, menthol is extensively used for thispurpose notwithstanding its strong minty odour and relative volatility.Other similar compounds have also been proposed as alternatives tomenthol in tobacco, see for example, the various publicationshereinbefore referred to. Still other compounds have been proposed as`flavourants` in tobacco rather than `coolants` and amongst these may bementioned 2-isopropyl-5-methyl hexanol (alternatively named2,6-dimethylhept-3-yl methanol) and related compounds as disclosed inU.S. Pat. No. 3,704,714. Notwithstanding these various disclosures aneed still exists for alternatives to menthol for incorporating intotobacco to provide a `cool` effect when smoked.

It is a further object of the present invention, therefore, to providetobacco and tobacco-containing manufactures containing an ingredientwhich creates a `cool` sensation when the ingredient comes into contactwith the nasal and oral mucosa, either in the tobacco smoke, or bydirect contact of the tobacco on the nasal or oral mucosa, but which arenot subject to the disadvantages of a strong minty flavour and storageinstability.

It is a yet further object of the present invention to provide animproved method of imparting to tobacco and tobacco-containingmanufactures a physiological cooling activity.

According to the present invention, therefore, there are also providedtobacco and tobacco-containing manufactures comprising tobacco and acold receptor stimulating additive, present in an amount effective tostimulate the cold receptors of the nervous system of mucous membranesof the oral and nasal mucosa when the tobacco or tobacco-containingmanufacture is smoke, chewed or inhaled by the human user, said additivebeing a cold receptor stimulating substituted methanol of the formulahereinbefore defined, subject to the following further proviso, namelythat when one of R¹ and R² is isoamyl and the other is isopropyl, thenR³ shall be C₁ -C₅ alkyl.

By tobacco and tobacco-containing manufactures we means any article,such as a cigarette or cigar, or any composition, such as pipe orchewing tobacco or snuff, containing tobacco in a prepared form readyfor utilisation by the human person whether by smoking, i.e. burning ofthe prepared tobacco and inhalation of the tobacco smoke, chewing ordirect inhalation of the tobacco.

In formulating the tobacco and tobacco-containing manufactures of thisinvention the active compound may be incorporated directly into thetobacco, for example, by impregnation of the tobacco with an alcoholicsolution of the active ingredient, at a suitable stage of manufacture.However, in an alternative and preferred arrangement, the activeingredient may be incorporated into a tobacco smoke filter for use in apipe or cigarette filter or as a filter tip for cigarettes. The latter,in particular, forms a particularly effective utilisation of the presentinvention, the active compound simply being impregnated in the wad ofmaterial forming the filter tip. This may be any of the well known typesof filter tip for cigarettes, e.g. a filter pad of cellulose acetate,paper, cotton, α-cellulose or asbestos fiber. Conveniently the filtertip is impregnated with an alcoholic solution of the active compound andthen dried to deposit the active compound therein.

The amount of active compound to be incorporated into the tobacco ortobacco-containing manufacture in accordance with the invention willvary from compound to compound depending on the activity thereof, i.e.the amount thereof which it is necessary to place in contact with theskin to produce a noticeable cooling effect, and will depend also on themode of application thereof, i.e. whether the compound is impregnated inthe tobacco itself, or in a filter tip or in any other accessory.However, the actual amount is not critical to this invention and will bereadily determinable by the person skilled in the art by means of a fewsimple tests. As a matter of guidance, however, it may be mentioned thatwith the more active compounds, as little as 0.01 mg deposited on thefilter tip of a tipped cigarette is effective.

This latter aspect of the invention is illustrated by the followingExamples.

EXAMPLE 21 Cigarette Tobacco

A proprietary brand of cigarette tobacco was sprayed with an ethanolicsolution of 2-methyl-3-ethylpent-3-yl methanol and was rolled intocigarettes each containing approximately 2.0 micrograms of activecompound. Smoking the impregnated cigarettes produced a cool effect inthe mouth characteristic of mentholated cigarettes but without anyattendant odour other than that normally associated with tobacco.

EXAMPLE 22 Filter Tip Cigarettes

The filter tip of a proprietary brand of cigarette was impregnated withan ethanolic solution of (1-isopropylcyclohexyl) methanol in an amountsufficient to deposit in the filter 0.02 mg of the active compound.Smoking the cigarette with the impregnated tip gave rise to a noticeablecooling effect in the mouth.

EXAMPLE 23 Pipe Tobacco

A proprietary brand of pipe tobacco was sprayed with an ethanolicsolution of (1-isopropyl-2-methylcycloheptyl) methanol 2g of the tobaccocontaining 12 mg of the active compound was placed in a pipe. Smokingthe impregnated tobacco produced a cool effect in the mouthcharacteristic of mentholated tobacco but without any attendant odourother than that normally associated with tobacco.

EXAMPLE 24 Cigars

The tobacco of a proprietary brand of cigar was impregnated with anethanolic solution of 2,2,4-trimethylpent-3-yl methanol in an amountsufficient to deposit in the cigar 2 mg of the active compound. Smokingthe cigar with the impregnated tobacco gave rise to a noticeable coolingeffect in the mouth.

EXAMPLE 25 Chewing Tobacco

A proprietary brand of chewing tobacco was impregnated with an ethanolicsolution of (1-isopropyl-2-methylcyclopentyl) methanol; 1g of thetobacco containing 1.0 mg of active compound was used. Chewing theimpregnated tobacco produced a cool effect in the mouth.

EXAMPLE 26 Snuff

A proprietary brand of snuff was impregnated with an ethanolic solutionof (2-isopropylcycloheptyl) methanol. 1g of the snuff was impregnatedwith 8 mg of active compound. About 0.01 g of the impregnated snuffproduced a cool effect in the nose when inhaled.

We claim:
 1. In a manufactured consumer product for application to orconsumption by the human body, said product comprising a topicallyadministrable or orally ingestible vehicle and, as adjuvants in saidvehicle, (i) at least one of the following: a flavourant, colourant,perfume, surface active agent or antiseptic, and (ii) a compound capableof stimulating the cold receptors of the nervous system in the surfacetissues of the body, or in the mouth, when brought into contacttherewith, respectively by topical application or oral ingestion of thesaid product, the improvement which comprises using as said coldreceptor stimulating compound an effective amount of an alcohol of theformula ##STR3## where R¹ is C₂ -C₆ alkyl;R² is C₂ -C₅ alkyl or C₂ -C₅alkenyl; R³ is H or C₁ -C₅ alkyl;with the provisos that the total numberof carbon atoms in the molecule is from 8-12 and that at least on of R¹and R² has branching in an alpha position.
 2. A product according toclaim 1 which is a personal care product containing an effective amountof said cold receptor stimulating compound.
 3. A product according toclaim 1 which is a chewing gum containing an effective amount of saidcold receptor stimulating compound.
 4. A method of stimulating the coldreceptors of the nervous system of the human body which comprisesapplying thereto an effective amount of an alcohol of the formuladefined in claim 1.